Diesel exhaust particle-induced alterations of pulmonary phase I and phase II enzyme systems.
Rengasamy-A; Barger-MW; Kane-E; Ma-JK; Castronova-V; Ma-JY
Toxicologist 2002 Mar; 66(1-S):126
Several environmental pollutants including polycyclic aromatic compounds induce carcinogenesis through the activation of xenobiotic metabolic pathways. The xenobiotics require bioactivation by phase I enzymes to induce carcinogenicity, while phase II enzymes contribute to resistance to chemical toxicity. The purpose of this study was to investigate the effects of diesel exhaust particle (Department) on phase I and phase II enzymes. Male rats were intratracheally instilled with saline (vehicle control) or a single dose of Department or carbon black (CB) at 5, 15, or 35 mg/kg body weight. CB was used as a control for the particulate carbon core of Department. At 1, 3, or 7 days post-exposure, lung microsomes and cytosol were prepared. The activities of CYP1A1 and CYP2B1 (Phase I enzymes) in microsomes and GST and catalase (phase II enzymes) in the cytosol were determined. Enzyme protein levels were determined by Western blot analysis. Department exposure at 5, 15, or 35 mg/kg, but not CB, significantly elevated CYP1A1 protein levels at 1 and 3 days post-exposure compared to the control. CYP1A1 activity was also increased with 15 and 35 mg/kg Department at 1 day post-exposure. On the other hand, both Department and CB exposures caused a significant decrease in CYP2B1 protein levels at 15 and 35 mg/kg with a concomitant attenuation of CYP2B1 enzyme activity. At 1 day post-exposure, both Department and CB significantly decreased the GST-Pi protein level at all doses tested with a significant attenuation in GST activity at 15 and 35 mg/kg. Catalase activity was significantly decreased by Department or CB (35 mg/kg) exposure at 1 and 7 days. These data suggest that the organic components of Department induce CYP1A1, while the carbon core attenuates CYP2B1, GST and catalase activities. The Department-induced alterations in the phase I and phase II enzyme pathways may play a significant role in pulmonary toxicity/carcinogenicity.
Diesel-exhausts; Pulmonary-system; Animal-studies; Exposure-levels; Pulmonary-cancer; Pulmonary-disorders; Animals; Laboratory-animals; Enzymes; Proteins; Exposure-levels; Exhaust-gases; Combustion-gases; Combustion-products; Particulates
Work Environment and Workforce: Mixed Exposures
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee